Identification of a Unique cyp51A Mutation in Aspergillus fumigatus from a Patient with Systemic Lupus Erythematosus and Limited Systemic Sclerosis: The First Report of Acquired Azole Resistance in Colombia - Report - MDSpire
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Identification of a Unique cyp51A Mutation in Aspergillus fumigatus from a Patient with Systemic Lupus Erythematosus and Limited Systemic Sclerosis: The First Report of Acquired Azole Resistance in Colombia
First Report of Acquired Azole-Resistant Aspergillus fumigatus in Colombia
Overview
A unique cyp51A mutation conferring azole resistance was identified in Aspergillus fumigatus isolated from a patient with systemic lupus erythematosus and limited systemic sclerosis in Colombia. This represents the first clinical case of acquired azole resistance reported in the country, highlighting emerging resistance in South America.
Background
Aspergillus fumigatus is a common environmental fungus that can cause severe infections primarily in immunocompromised patients. Azole antifungals, especially voriconazole, are first-line treatments, but resistance is increasingly reported worldwide. Resistance mechanisms often involve mutations in the cyp51A gene, with TR34/L98H and TR46/Y121F/T289A being the most common globally. Surveillance data on azole resistance in South America remain limited, making this case significant for regional epidemiology.
Data Highlights
Parameter
Value
Normal Range
Leukocytes
14,330 - 23,760 cells/µl
4,500 - 11,000 cells/µl
Neutrophils
12,190 - 21,650 cells/µl
1,500 - 8,000 cells/µl
C-Reactive Protein (CRP)
21.1 - 24.12 mg/L
<10 mg/L
D-dimer
1.98 µg/mL
<0.5 µg/mL
Serum Aspergillus Galactomannan Antigen
1.65 - 3.83 initially, then 0.57
<0.5 negative
Voriconazole MIC
>32 µg/ml
Susceptible <1 µg/ml
Itraconazole MIC
>1 µg/ml
Susceptible <1 µg/ml
Key Findings
A 29-year-old female with overlap syndrome (SLE and limited SSc) developed chronic pulmonary aspergillosis treated initially with voriconazole.
Despite prolonged voriconazole therapy, Aspergillus galactomannan antigen remained positive and clinical symptoms worsened.
A. fumigatus isolate from bronchoalveolar lavage showed a novel cyp51A mutation combination: TR46/F46Y/Y121F/M172V/E427K.
The isolate exhibited high-level resistance to voriconazole (MIC >32 µg/ml) and itraconazole (MIC >1 µg/ml).
The patient progressed to invasive aspergillosis and died despite switching to caspofungin therapy.
This is the first documented case of acquired azole resistance in A. fumigatus in Colombia, expanding the known resistance mutations in South America.
Clinical Implications
Clinicians should consider azole resistance in patients with persistent or worsening aspergillosis despite appropriate therapy, especially in immunocompromised hosts. Routine antifungal susceptibility testing and molecular characterization of A. fumigatus isolates may guide effective treatment. Awareness of emerging resistance patterns in South America is critical for optimizing antifungal stewardship and patient outcomes.
Conclusion
This case highlights the emergence of a novel azole-resistant A. fumigatus strain in Colombia with a unique cyp51A mutation profile, underscoring the need for enhanced surveillance and susceptibility testing in the region. Early detection of resistance can inform timely therapeutic adjustments to improve prognosis.
References
Article Source 2025 -- Identification of a Unique cyp51A Mutation in Aspergillus fumigatus from a Patient with Systemic Lupus Erythematosus and Limited Systemic Sclerosis
by Carlos Morales-Pertuz, Miguel Ángel Vanegas, Ximena Castañeda-Luquerna, Eliana Maldonado, Jorge Alberto Carrillo, Anghie Katherine López-Valencia, Carolina Firacative
